Method and apparatus for measuring pulmonary blood flow by pulmonary exchange of oxygen and an inert gas with the blood

ABSTRACT

A method and apparatus for measuring pulmonary blood flow in a subject by pulmonary exchange of oxygen and an inert gas with the blood using a divided respiratory system. One method of isolating two or more divisions of the respiratory system uses a multi-lumen cuffed endobronchial catheter. In one embodiment, a triple-lumen cuffed endobronchial catheter is provided. In another embodiment, gas mixtures are supplied to each lumen using a bag-in-a-box type ventilator for each breathing system for synchronizing the rate and pressure of mixed gas supplied to the lumens.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. patentapplication Ser. No. 09/530,084, filed Jun. 27, 2000, now pending, whichis a PCT conversion into the U.S. National phase of PCT/AU97/00717,filed Oct. 24, 1997, now published as WO 98/18383, which claims priorityfrom Australian application number PO 3223 filed Oct. 25, 1996, whichapplications are incorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] This invention relates to the measurement of blood flow in asubject, more particularly to a method and apparatus for measuringpulmonary blood flow by pulmonary exchange of oxygen and an inert gaswith the blood utilizing a divided respiratory system. The invention isespecially suitable for monitoring pulmonary blood flow/cardiac outputof a patient under general anesthetic and accordingly it will beconvenient to described the invention in connection with thisapplication. However, it is to be understood that the method andapparatus described herein may be used for determining the pulmonaryblood flow or cardiac output of a subject in a conscious state.

[0004] 2. Description of the Related Art

[0005] The equation that links the cardiac output of a subject to moredirectly measured parameters is as follows:

{dot over (U)} _(gas) ={dot over (Q)} _(c)λ(F _(Agas) −F _(Vgas))

[0006] where F_(Agas) refers to the concentration of inert soluble gasin the alveolar gas mixture of the lungs expressed as fraction of itspartial pressure to the barometric pressure (Bp),

[0007] F_({overscore (V)}gas) refers to the fraction of the inertsoluble gas in the mixed venous blood expressed as a fraction of itspartial pressure to the total pressure,

[0008] λ is the Ostwald solubility coefficient of the inert soluble gasin blood,

[0009] {dot over (Q)}_(c) is the cardiac output that passes through thepulmonary capillaries in the walls of gas containing alveoli, and

[0010] {dot over (U)}_(gas) is the uptake into the blood from thealveoli measured in units of volume at body temperature arid barometricpressure per unit time.

[0011] This equation holds true for inert gases only. In this regard aninert gas dissolves in blood proportionally to its partial pressure i.e.it obeys Henry's Law. By contrast a reactive gas does not obey Henry'sLaw by reason of its reacting chemically with blood constituents. Oxygenand carbon dioxide are examples of reactive gases.

[0012] The term cardiac output as used herein refers to the amount ofblood per unit time which passes through the pulmonary capillaries inthe walls of the alveoli of the lungs. If hemoglobin O₂ saturation ofthe subject is 100% then the whole cardiac output will be equivalent tothe pulmonary blood flow, i.e. the amount of oxygenated blood passingthrough the pulmonary capillaries in the walls of the alveoli of thelungs. If this saturation is less than 100% the whole cardiac outputincludes shunt blood in addition to pulmonary blood flow. Shunt blooddoes not transport O₂ from the lungs to the tissue and may therefore beignored. The % shunt may be estimated from pulse oximetry.

[0013] Most methods in use today or described in the literature refer toor depend on the above equation, but F_(Vgas) cannot be measuredaccurately without obtaining a sample of mixed venous blood, which wouldsacrifice the advantage of non-invasiveness of large blood vessels withcatheters, as is necessary with the most widely used method of measuringcardiac output presently in use, namely the thermodilution method.

[0014] Most gas exchange methods for measuring the cardiac output whichhave been attempted suffer from the problem of “recirculation” whichlimits them to only intermittent determinations of {dot over (Q)}_(c)separated by relatively long intervals to wash out gas introduced by theprevious determination. This restriction of frequency of taking readingsof {dot over (Q)}_(c) is necessary to ensure that P_({overscore (V)}gas)has returned to a value close to zero before another determination isperformed. The same constraint also applies to methods using reactivegases. The term “recirculation” refers to the return back to the lungsin the mixed venous blood of gas that has previously been taken awayfrom the lungs in the arterial blood.

[0015] It is an object of the present invention to overcome or at leastalleviate one or more of the abovementioned difficulties of the priorart, or at least to provide the public with a useful choice.

BRIEF SUMMARY OF THE INVENTION

[0016] Accordingly, in a first aspect the present invention provides amethod for measuring the pulmonary blood flow in a subject including:

[0017] isolating two or more divisions of the respiratory system, saiddivisions comprising the complete gas exchanging part of saidrespiratory system,

[0018] ventilating each said division with a separate gas mixture, atleast one of said gas mixtures including an inert soluble gas,

[0019] determining uptake of inert soluble gas in at least two of saiddivisions,

[0020] determining uptake of oxygen in each of said divisions,

[0021] determining end tidal concentration of inert soluble gas in atleast two of said divisions, and

[0022] calculating pulmonary blood flow from determined values of uptakeand end tidal concentration of inert soluble gas, and relative pulmonaryblood flow.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

[0023] The invention will now be described with reference to someexamples and drawings which illustrate some preferred aspects of thepresent invention. However it is to be understood that the particularityof the accompanying examples and drawings is not to supersede thegenerality of the preceding description of the invention.

[0024]FIG. 1 is a perspective view of a triple lumen, cuffedendobronchial catheter according to the invention.

[0025]FIG. 2 is a partial cross sectional view of the triple lumencatheter of FIG. 1 inserted in the respiratory system of the subject.

[0026]FIG. 3 is a diagrammatical representation of apparatus useful forthe measurement of pulmonary blood flow in a subject.

DETAILED DESCRIPTION OF THE INVENTION

[0027] Preferably two or three divisions of the respiratory system areisolated, most preferably three divisions.

[0028] When three divisions are isolated it is preferred that two of thedivisions are ventilated with gas mixtures which are substantiallybalanced with respect to inert soluble gas, the concentration of inertsoluble gas in each of these two divisions being different from eachother, and the third division is ventilated with a gas mixture which isunbalanced with respect to inert soluble gas.

[0029] One method of isolating two or more divisions of the respiratorysystem utilizes a multi-lumen cuffed endobronchial catheter.

[0030] Accordingly in a second aspect of the invention there is providedapparatus for measuring pulmonary blood flow in a subject including:

[0031] a multi-lumen cuffed endobronchial catheter adapted to allowseparate gas mixtures to be provided to two or more separate divisionsof the respiratory system of the subject, said separate divisionscomprising the complete gas exchanging part of said respiratory system,

[0032] two or more breathing systems for supplying different mixtures toeach lumen of said multi-lumen catheter at the same rate and the sametotal pressure,

[0033] two or more gas delivery systems for providing gas mixtures tosaid two or more breathing systems,

[0034] sampling means for sampling (i) inspired and expired gas in eachdivision and/or (ii) the fresh flow gas and the exhaust gas of eachdivision, and

[0035] gas analyzer for determining concentrations of gases in saidsamples,

[0036] a flow determining means for determining flow rates of (i) saidinspired and expired gas and/or (ii) said fresh flow gas and exhaust gasand,

[0037] processing system for calculating pulmonary blood flow from saiddetermined concentrations and flow rates.

[0038] One method of ensuring that the gas mixtures are supplied to eachlumen at the same rate and the same total pressure is to use abag-in-a-box type ventilator with each breathing system, and operate theventilator by supplying a common working gas. Other methods forsynchronizing the rate and pressure of mixed gas supplied to the lumensof the catheter would be evident to a person skilled in the art.

[0039] It is to be noted that the defined apparatus is not essential foruse of the method of measurement defined above, but represents aparticularly convenient apparatus useful in making the requiredmeasurements.

[0040] Endobronchial catheters having more than two lumens are novel andrepresent a third aspect of the present invention. Particularly accurateresults can be obtained if the multi-lumen cuffed endobronchial catheterhas three lumens.

[0041] Accordingly in a fourth aspect of the invention there is provideda triple lumen, cuffed endobronchial catheter for providing separate gasmixtures to each of three separate divisions of the respiratory systemof a subject, said three divisions comprising the complete gasexchanging part of said respiratory system, said catheter comprising:

[0042] a primary tube having three lumens adapted to be inserted withinthe trachea of a subject, each of said lumens opening at a top endthereof into a connector tube adapted to be connected to a breathingsystem, and opening at a bottom end thereof into an outlet fordelivering a gas mixture to one of said divisions,

[0043] one or more inflatable cuffs located about said primary tubeand/or said outlets adapted to form seals within the respiratory systemsuch that each outlet is capable of delivering a gas mixture to one ofsaid three separate divisions in isolation from each of the otherdivisions.

[0044] The outlet may be an opening in a tube, or a short tube with anopening, for delivering a gas mixture to a division of the respiratorysystem from a lumen of the primary tube. The outlet may be an extensionof a lumen of the primary tube or may be an opening in the bottom end ofa lumen.

[0045] The triple lumen cuffed endobronchial catheter preferably has aninflatable cuff located about the primary tube and above the outletswhich is adapted to form a seal within the trachea.

[0046] In a particularly preferred embodiment the triple lumen catheterincludes a first inflatable cuff as described above in combination witha second inflatable cuff located between the first and third outlets forforming a second seal in the right bronchus and a third seal in thehyparterial bronchus, the third seal allowing the third outlet toprovide a gas mixture to the middle and lower lobes of the right lungand the second and third seals together allowing the second outlet toprovide a gas mixture to the upper lobe of the right lung.

[0047] The second inflatable cuff preferably encircles the second outletand lies within the right main bronchus and the hyparterial bronchus.

[0048] It is also possible to manufacture triple lumen catheters withinflatable cuffs as described above which are adapted to supply gasmixtures to the right lung, the upper lobe of the left lung and thelower lobe of the left lung, although for technical reasons it is lessconvenient.

[0049] According to the present invention the measurement of pulmonaryblood flow or cardiac output can be made at short intervals for anextended period of time, while avoiding the problems of recirculation.The measurements can be made rapidly and the calculations may beperformed using appropriate software on a computer.

[0050] Anesthesia is normally given through a single anestheticbreathing system, however the present invention involves the use of morethan one breathing system. Satisfactory results are obtainable with twobreathing systems, however more accurate results can be obtained withthree. Further improvement is theoretically possible with more thanthree breathing systems.

[0051] Each breathing system delivers to the subject its own individualadjustable ventilating gas mixture to one division of the subject'salveolar volume through its particular branch of the bronchial tree.

[0052] Such a set-up ensures that every part of the total alveolar gasvolume (i.e. the complete gas exchanging part of the respiratory system)was being ventilated through one or other of the airway divisions, butno part was being ventilated through more than one airway division. Thenumber of such divisions which is possible is only limited by technicalconsiderations.

[0053] The simplest example of such an arrangement, readily achievablewith existing anesthetic equipment, has two such divisions, namely theleft lung and the right lung.

[0054] After placement of a conventional endobronchial double-cuffed,double-lumen catheter (a “double lumen tube”—e.g. Bronchocath orRobertshaw type) the left lung and the right lung may each be ventilatedwith entirely separate gas mixtures administered through entirelyseparate breathing systems each served by its own separate fresh gassupply by a dedicated gas delivery system. Alternatively a custom madedouble lumen tube which ventilates (1) the right upper lung lobe and (2)the remainder of the respiratory system could readily be designed alongthe lines of previously mentioned triple lumen tube but with combinedfirst and third lumens.

[0055] The subject on whom this method is being used to determine thecardiac output might be, by way of example, a patient undergoing generalanesthesia and the inert gas might be nitrous oxide (N₂O). In this caseN₂O, being an anesthetic drug, is contributing to the patient'sanesthetic state, but this need not necessarily be so for other inertgases.

[0056] In this case the total alveolar volume is divided into twodivisions, namely the left lung and the right lung and the airway islikewise divided into two divisions, one for each lung.

[0057] Each lung is then ventilated with a gas mixture supplied to it byits own breathing system. Any workable breathing system would suffice.In a typical arrangement used for general anesthesia there would beinflow into the breathing system of component gases under the control ofthe anesthetist by a needle valve for each. In this case two of thecomponents would be O₂ (used in all cases) and N₂O. The anesthetistgenerally observes the flow rate of each gas flow he controls by meansof a gas rotameter or other continuously measuring flowmeter.

[0058] The breathing systems may contain fresh canisters of soda-lime toabsorb the CO₂ produced by the patient, for example semi-closed orclosed circle absorber systems (SCCA or CCA). Alternatively they may notcontain soda-lime, e.g. Mapleson systems A to E. A preferred type is theHumphrey ADE low-flow multipurpose breathing system, adaptable to bothsoda-lime absorption or to Mapleson A or Mapleson D systems withoutsoda-lime. (An advantage of this make is a low circuit volume madepossible by its flexible-tube design. It can also be readily convertedfrom spontaneous breathing mode to IPPV mode by flicking a switch.)

[0059] The most preferred type is the non-rebreathing system whereby thefresh gas flow from the gas delivery system is also the inspiratory gasand the expiratory gas is the same as the exhaust gas.

[0060] Except in a completely closed system every breathing systempossesses a spill-valve to vent excess gas, i.e. exhaust gas, from thecircuit either under manual control or acting automatically.

[0061] Each breathing system may connect to the external opening of oneof the lumens of the multi-lumen endobronchial catheter, usually via aconnector tube, which may include a catheter mount. Breathing system gaspasses into the patient with each inspiration, and expired gas the otherway during expiration.

[0062] The preferred form of the invention employs three breathingsystems and three divisions of the respiratory system.

[0063] One method of doing this entails the use of a small diametercuffed flexible catheter passed down one or other lumen of the doublelumen tube. It is pushed down into the lung until it will go no furtherand the cuff inflated with a minimum volume of air or fluid. The top endcomes out near the top end of the larger tube through an opening in itsside, ensuring there are no leaks from the larger tube at the point ofexit. The small tube ventilates a segment of one lung and the largertube the remainder of that lung. The other lumen of the double lumentube functions as described in relation to the double lumen systemdescribed above.

[0064] A similar procedure can be carried out with two such smallcatheters passed through a cuffed endotracheal tube.

[0065] The small diameter cuffed flexible catheter may be, for example,a Foley's urinary catheter or a Swan-Ganz catheter or similar orcustom-made type.

[0066] The preferred form of subdividing ventilation of the alveolarvolume into three divisions consists of a custom-made preformedtriple-lumen catheter analogous in structure to a double lumen tube.This is termed a “triple lumen tube” or “triple lumen catheter”.

[0067] A triple lumen tube is preferred to the three-division methodsdescribed above because its position in the patient's bronchial tree canbe checked by fibreoptic bronchoscopy whereas a cuffed flexible catheteris placed blindly and is also prone to migration after placement becauseof its flexibility. This may result in occlusion of the opening of abronchus that branches off the lumen of the bronchus in which theinflated cuff of the catheter lies. This, will cause collapse of asegment of a lung. Though this may happen without serious immediateeffects, in the presence of lung pathology it could possibly cause e.g.local infection or other local pathology in the longer term.

[0068] The following parameters may be monitored using techniques knownto the art, e.g. using appropriate gas sampling and analyzing equipment.

[0069] (i) The uptake or excretion of one or more of the gas species bythe subject, from the fresh gas flow, “FGFgas”, between its point ofentry into the system and its point of exit from the system in theexhaust gas flow, “EXHgas”.

[0070] (ii) The end-tidal concentrations of one or more of the inertsoluble gases present.

[0071] In a preferred embodiment the uptake or excretion of eachseparate gas species from each breath is measured at the external end ofthe divisional lumen of the endobronchial tube. The term “breath” asused herein refers to one respiratory cycle. The term “uptake” as usedherein refers to both uptake and excretion, excretion being a negativevalue of uptake.

[0072] This latter measurement considerably improves the response timeof the cardiac output measurement, i.e. its responsiveness to transientor rapid changes of the cardiac output, but the cardiac output couldstill be measured, though with a slower response time if this lattermeasurement were omitted.

[0073] The arrangement described below follows the usual anestheticequipment pattern:

[0074] Each divisional alveolar volume may be served, from abovedownward, by a gas delivery system, consisting of separate sources ofgas flow, one for each type of gas, each with a flow control and, forsafety reasons, a visual monitor of the instantaneous flowrate of eachof the separate gas flows. These gas flows are joined together in asingle mixed flow and pass to a breathing system. The breathing systemallows the inspiratory gas mixture to enter and leave the divisionalalveolar volume either by normal breathing action, or (preferred) by theaction of a ventilator. The exhaust gas leaves the breathing system atsome point in it. The preferred point of exit is from the ventilatorreservoir bag (concertina bag) in the case of the bag-in-a-box typeventilator.

[0075] Gas in the breathing system enters one lumen of a multi-lumentube, there being one lumen for each gas delivery system/breathingsystem combination, and enters the divisional alveolar volume duringinspiration. It leaves again during expiration. As it enters and exitsthe tube lumen the gas may be sampled and analyzed at a continuous smallrate. Where a separate flow measuring device is in use for measuringbody uptakes, it is also preferably located here. For whole systemuptakes, sampling for gas analysis and separate flow measurement devicesmay be at two locations—(1) in the gas delivery system, between theunion of flows of separate gas flows and the common gas outlet and/or(2) in the tube leading away exhaust gas.

[0076] Whether uptakes are being measured between divisional FGFgas andEXHgas (whole system uptakes) or between the divisional inspiratory flowand expiratory flow of every breath (body uptakes) there is a range ofways by which these uptake measurements can be made.

[0077] The advantage of measuring body uptakes over whole system uptakesis that the response time is faster because the only volume bufferingchange is the divisional respiratory system volume. In the case of wholesystem uptakes the volume buffer also includes the volume of thedivisional breathing system.

[0078] The advantage of measuring whole system uptakes is that they aremore easily performed because thorough mixing of the gas flows can bemore easily secured and therefore greater accuracy is achieved.

[0079] As there is a trade-off between the advantages, the preferredarrangement is to measure whole system uptakes and body uptakes incombination. This allows an optimum resultant accuracy and response.

[0080] Examples of methods for measuring the necessary uptakes are givenbelow. Each of these methods may be applied to either whole systemuptakes or body uptakes, and either in whole or in part. The term“inflow” applies either to divisional FGFgas or to divisionalinspiratory flow in this section according to context, and similarly“outflow” applies to EXHgas or to divisional expiratory flow.

[0081] The use of Flow Measuring Devices

[0082] Examples of flow measuring devices include the pneumotachograph,the hot wire anemometer and the turbine anemometer. Other devices whichmeasure gas flow accurately are also suitable.

[0083] The response time of the flow measuring device is relevant if theflow of gas changes over time. The response time is preferably such thatthe device is capable of following flow changes closely. Incompatibleresponse times will result in even longer uptake measurement times inthe case of whole system uptakes. Contamination will occur betweeninspiratory end expiratory measurements in the case of body uptakesrendering them useless unless special breathing circuitry is employed.

[0084] In this regard inspiratory and expiratory sampling lines may beconnected between the inspiratory and expiratory limbs respectively ofan IPPV breathing system and a gas analyzer. Sampling and analysis ofthe gas mixtures could be coordinated with the ventilator such thatsampling and analysis of the inspired gas is triggered when theventilator is in its inspiratory phase and vice versa. This could beachieved by an appropriate combination of solenoid valves on thesampling lines which are operated by a solenoid control unit which iscoordinated with the ventilator operation.

[0085] Where the instrument response time is compatible with flowchanges, the rapid response of the flow measuring device may be used inconjunction with a rapid gas analyzer (RGA) to yield flowrate signals ofindividual gas species ({dot over (V)}_(x)).

[0086] For example a digitized signal stream from an RGA sampling thegas mixture can represent individual values of F_(x) (the fractionalconcentration in the gas mixture of gas x). This stream may be combinedwith a corresponding stream of {dot over (V)}_(I) or {dot over (V)}_(E)signals representing instantaneous inspiration or expiration signalsrespectively from such a flow measuring device such that each signalfrom the RGA corresponds in time with a signal from the device. By acomputational process the F_(x) signals from the RGA may be multipliedby the corresponding {dot over (V)}_(I) or {dot over (V)}_(E) signalsfrom the device to form a resultant stream of signals, each representingthe instantaneous flowrate of x into or out of the subject's divisionalairway and alveolar volume, {dot over (V)}_(Ix) or {dot over (V)}_(Ex).Integration of this resultant stream of signals over the time intervalof measurement, t, gives the volume of x that has passed over this timeV_(TIx) or V_(TEx).

[0087] The time interval chosen is conveniently the duration ofinspiration or the duration of expiration in the case of body uptakes,the instrument detecting the changeover moment from inspiration toexpiration as the moment of zero flow separating positive (inward)values of flow from negative (outward) ones.

[0088] If the inward passing and outward passing volumes of x are thusmeasured with each breath then the difference between them is the uptakewith each breath, U_(Tx). The rate of uptake of x, {dot over (U)}_(x),is U_(Tx), multiplied by the respiratory rate, RR. Alternatively {dotover (U)}_(x) may be determined more directly by taking the average of({dot over (V)}_(ix)−{dot over (V)}_(Ex) evaluated over an integralnumber of respiratory cycles.

[0089] Algebraically:

{dot over (V)} _(1x) =F _(x) ·{dot over (V)} ₁ and {dot over (V)} _(Ex)=F _(x) ·{dot over (V)} _(E)

V _(TIx)=_(o)∫^(t) {dot over (V)} _(1x) and V _(TEx)=_(o)∫^(t) {dot over(V)} _(Ex)

U _(Tx) =V _(TIx) =V _(TEx)

{dot over (U)} _(x) =U _(Tx) ·RR

[0090] The use of an Insoluble Gas to Measure Flow

[0091] An insoluble gas, “marker gas”, can be added at a steady knownflowrate, {dot over (V)}_(marker), to an inflow, is allowed to mixradially and is then sampled periodically by a gas analyzer. The totalflow rate of gas, {dot over (V)}_(I) is:

{dot over (V)} _(E) ={dot over (V)} _(marker) /F _(Imarker)

[0092] where F_(Imarker) is the fractional concentration of marker gasmeasured.

[0093] If the sampling rate and the analyzer's response time aresufficiently fast the {dot over (V)}_(I) signals may be used in exactlythe same way as the {dot over (V)}_(I) signals generated by a flowmeasuring device and uptakes of any gas of interest may be measured on abreath to breath basis.

[0094] To achieve this end, expiratory flows are most convenientlymeasured by using a second marker gas (another species of insolublegas). In one arrangement a single sampling point not far beyond theexternal end of the divisional lumen of the multi-lumen tube may beflanked by two marker gas delivery ports to the airway, one on eachside. The distance between each port and the sampling point issufficient to allow radial mixing of marker gas in the gasflow.

[0095] Marker gases may be any non-toxic insoluble gas. Examples of sucha gas include helium, nitrogen, argon, sulfur hexafluoride, neon andmany others. It may be used in any convenient concentration taking intoaccount body tissue stores in the case of a gas found naturally in theatmosphere. This applies particularly to nitrogen but if traceconcentrations are to be used it may apply to other gases as well.

[0096] Volume Displacement Devices

[0097] V_(TI) may be measured this way. A piston pump is an example whenused as a ventilator when due correction is made for compliance withinthe breathing system. Another more common example is the concertina bagof a bag-in-a-box ventilator where the volume of gas delivered by thebag can be regulated by a mechanical stop inside the box. V_(TE) mayalso be measured by volume displacement whereby a spirometer for examplemay be used, or the concertina bag may be caused to function like aspirometer. Spontaneously breathing patients may breathe into and out ofa spirometer. In all these cases, spirometer or bag displacement may betransduced into an electrical signal for the purposes of furthercalculations.

[0098] Mixing Devices

[0099] F_(marker) and F_(x) measurements may be considerably simplifiedif discrete volumes of gas are mixed longitudinally before measurementbecause then complex mathematical processes and fast response times canbe dispensed with.

[0100] Mixing may be performed by passing the flows of gas throughmixing boxes, or by stirring them by e.g. a fan, or employing othersimilar means of either mechanical baffles or active mixing.

[0101] Constraining to Uniform Flowrate

[0102] If inspiration and expiration occur at a constant flowrate and asufficiently large number of gas analyses are made during the course ofa single breath, simple inspiratory or expiratory averaging of multiplevalues for F_(marker) and F_(x) simplifies the calculation of masstransfer because unit time in this case is exactly equivalent to unitvolume.

[0103] Suggested Gas Analysis Techniques

[0104] Gas concentrations may be measured by any suitable technique buta form of rapid gas analysis may provide the best data by reason of (a)rapid response rate to change and (b) by averaging, giving a moreprecise determination. Suitable RGA devices include mass spectrometers,infrared spectrometers, photoacoustic devices, paramagnetic andparamagnetic acoustic devices and Raman scatter analyzers.

[0105] Calculation of {dot over (Q)}_(c)

[0106] The ratios of O₂ uptakes of subdivisions of the total alveolarvolume are assumed to accurately reflect their relative pulmonary bloodflows. This will certainly be true if pulse oximetry shows a highhemoglobin O₂ saturation (e.g. 95%-100%). (Pulse oximetry is universallyused as a monitoring modality for severely ill and anaesthetizedpatients.) If the hemoglobin O₂ saturation is not high the ratiosrepresent flows of oxygenated blood through the subdivisions.

[0107] From the foregoing measurements and the end-tidal F_(AN) ₂ _(O)values, {dot over (Q)}_(c) can be calculated as follows.

[0108] The calculations will be illustrated by reference to the twodivision model previously outlined but corresponding equations exist toapply to any number of divisions. For the purpose of the followingmathematical discussion N₂O will be used as the type gas but any solubleinert gas “x” will also give a valid result.

[0109] The uptakes of N₂O ({dot over (U)}_(N2) _(^(OL)) and {dot over(U)}_(N2) _(^(OR)) ) for the left and right lungs respectively aregoverned by their respective alveolar fractional partial pressures ofN₂O (F_(AN) ₂ _(OL) and F_(AN) ₂ _(OR)), the mixed venous fractionalpressure of N₂O (F_({umlaut over (V)}N) ₂ _(O)), the Ostwald solubilitycoefficient for N₂O, λ, and the respective lung shares of the cardiacoutput ({dot over (Q)}_(cL) and {dot over (Q)}_(cR)):

{dot over (U)} _(N) ₂ _(OL) ={dot over (Q)} _(cL)λ(F _(AN) ₂ _(OL) F_({overscore (V)}N) ₂ _(O))  1

{dot over (U)} _(N) ₂ _(OR) ={dot over (Q)} _(cR)λ(F _(AN) ₂ _(OR) F_({overscore (V)}N) ₂ _(O))  2

[0110] The respective uptakes in the left and right lungs are measuredsimultaneously so that F_({overscore (V)}N) ₂ _(O) is the same in each.

[0111] The most effective values to use for F_(AN) ₂ _(OR) and F_(AN) ₂_(OL) are when the two values are as widely separated from each other aspossible, in order to maximize N₂O transfer in the lungs and therebymake N₂O uptake measurements more precise. Preferably one lung isventilated with a gas mixture containing 60% to 80% of N₂O (solubleinert gas) while the other lung is ventilated with a gas mixturecontaining 0-20% N₂O, preferably 0%. More preferably one lung isventilated with a gas mixture containing$\frac{{{Bp}({mmHg})} - 150}{{Bp}({mmHg})} \times 100\% \quad N_{2}O$

[0112] while the other lung is ventilated with a gas mixture containingno N₂O.

[0113] Preferably there is positive uptake in one lung and negativeuptake (excretion) in the other lung.

[0114] The ratio of the respective oxygen uptakes, {dot over (U)}_(O) ₂_(R) and {dot over (U)}_(O) ₂ _(L), equals the {dot over (Q)}_(cR) to{dot over (Q)}_(cL) ratio:

{dot over (Q)} _(cR) /{dot over (Q)} _(cL) ={dot over (U)} _(O) ₂ _(R)/{dot over (U)} _(O) ₂ _(L)  3

[0115] This can be shown as follows:

[0116] Under anesthesia there could be areas of the lung that are poorlyventilated so that the hemoglobin of the blood passing through such anarea is less than 100% saturated with oxygen when it passes on into thearterial system.

[0117] The “SpO₂” measures the saturation in the arterial system and isa universal monitor. If the SpO₂ indicates that the hemoglobin issaturated (SpO₂=100%) this indicates there are no poorly ventilatedareas. If this is the case (which is usual) the uptake of oxygen fromany given area of the lung, or from the right lung to the left lung isstrictly proportional to the blood flow through that area of lung.Accordingly, a method of determining the relative pulmonary blood flowthrough an area o flung is to measure the relative oxygen uptakes.

[0118] This statement is not true for the uptake of N₂O or any other gasthat does not saturate a carrier molecule such as hemoglobin. In thesecases less N₂O is taken up by poorly ventilated areas than by wellventilated ones even if the respective blood flows are equal, becauseN₂O obeys Henry's Law and less of it dissolves in blood when there isless in the alveolar gas, more of it when better regional ventilationproduces more in the alveolar gas of that region.

[0119] To summarize when O₂ fully saturates its carrier moleculehemoglobin, its concentration in blood is always the same. All mixedvenous blood returning to the heart from the rest of the body has thesame level of desaturation at a particular moment in time (usually about75%). Therefore the uptake of O₂ from particular places in the lung mustdepend on the blood flow rate to that place and only on this whereas forN₂O, which obeys Henry's Law, uptake will depend both on the regionalblood flow rate and on the regional concentration of N₂O in the regionalalveolar gas.

[0120] Therefore equations 1, 2 and 3 above are simultaneous and containthree unknowns, namely {dot over (Q)}_(cR), {dot over (Q)}_(cL) andF_({overscore (V)}N) ₂ _(O).

[0121] Now:

{dot over (Q)} _(c) ={dot over (Q)} _(cL) +{dot over (Q)} _(cR)

[0122] The calculations can be carried out on line by a computer.

[0123] The above set of simultaneous equations, lead when solved to thefollowing equation: $\begin{matrix}{{\overset{.}{Q}c} = \frac{{{\overset{.}{U}}_{N_{2}{OL}}\left( {1 + \frac{{\overset{.}{U}}_{O_{2}R}}{{\overset{.}{U}}_{O_{2}L}}} \right)} - {{\overset{.}{U}}_{N_{2}{OR}}\left( {1 + \frac{{\overset{.}{U}}_{O_{2}L}}{{\overset{.}{U}}_{O_{2}R}}} \right)}}{\lambda \left( {F_{{AN}_{2}{OL}} - F_{{AN}_{2}{OR}}} \right)}} & 4\end{matrix}$

[0124] The assertion above that the most effective values for F_(AN) ₂_(OR) and F_(AN) ₂ _(OL) are when the two values are as widely separatedfrom each other as possible can be demonstrated with the help of thisequation. The values of F_(AN) ₂ _(OL) and F_(AN) ₂ _(OR) being aswidely separated is achieved when F_(IN) ₂ _(OL) and F_(IN) ₂ _(OR) willbe as widely separated as possible also, F_(IN) ₂ _(OL) and F_(IN) ₂_(OR) being the inspired fractional N₂O concentration in the left andright lungs respectively. (F_(AN) ₂ _(OL) and F_(AN) ₂ _(OR) aremeasured by the RGA as the concentration of N₂O in the expired gas atthe end of expiration.)

[0125] As these two values become less widely separated the quantity(F_(AN) ₂ _(OL)−F_(AN) ₂ _(OR)) becomes smaller. As this is thedifference between two measured quantities the relative error of thisdifference becomes greater and greater, tending toward infinity as(F_(AN) ₂ _(OL)−F_(AN) ₂ _(OR)) tends towards its lower limit of zero.Therefore the error of {dot over (Q)}_(c) also approaches infinity asthe end expiratory concentrations of N₂O become equal to each other inthe two divisional alveolar volumes (which in this case are the leftlung and the right lung).

[0126] More than one soluble inert gas may be used in the gas mixture.In this case it is possible to calculate the cardiac output by the twoseparate sets of results and then combine the measured cardiac output ofeach inert gas calculation into a single value by weighting eachaccording to its estimated margin of error in the appropriate manner.These calculations are preferably carried out by a computer.

[0127] The double lumen endobronchial cuffed tube may be modified into atriple lumen tube. The third lumen may serve the right upper lobebronchus or the left upper lobe bronchus.

[0128] One advantage of a third lumen is that it may be ventilated withair or a gas mixture containing insoluble gas. The inflow of fresh gasto a closed circle breathing system without soda-lime that is connectedto the third lumen (third division of the respiratory system), could becut off for prolonged periods because uptake from it would be very slowbecause of the presence of insoluble gas. (Any gas removed from thissystem through sampling needs to be replaced with insoluble gas or air.)The mixed venous partial pressure of each gas dissolved in mixed venousblood would rapidly come into equilibrium with the gas in therebreathing system of the third lumen, from which soda-lime is omittedso CO₂ is also in equilibrium. In this way the mixed venous tensions ofall relevant gases, which would be of interest and value to theanesthetist in their own right, could be given to him. This can be doneby ventilating the division and sampling of end-tidal gas. In addition adirect knowledge of the partial pressure fraction of the soluble inertgas in the mixed venous blood would increase the accuracy of the {dotover (Q)}_(c) determination when compared with the independentdetermination calculated as in the foregoing equations, and used tocorrect it.

[0129] A further advantage of a third lumen is that it can reduce errorsassociated with a phenomenon called {dot over (V)}/{dot over (Q)}mismatch.

[0130] A theoretical assessment of the error associated with thepulmonary blood flow measurement indicates that the major source oferror is likely to reside in {dot over (V)}/{dot over (Q)} mismatch.

[0131] This is an imperfection in lung physiology which essentiallyimplies a failure to match the ventilation of every portion of the lungexactly to its perfusion with blood.

[0132] The term “perfusion” refers to the flowrate of blood through unitvolume of lung. Normally the lung is perfused with blood rather unevenlysuch that the most dependent parts of the lung, i.e. the lower parts,have a higher perfusion than those not so dependent. A change in bodyposition means that any particular small region of the lung willprobably change its perfusion by reason of changing its verticaldistance from the heart, which is the controlling factor. Thedistribution of blood flow throughout the lungs will change.

[0133] Along with this there is also a change in the regionaldistribution of ventilation which quite closely matches the change inblood flow. Normally all parts of the lung have a ratio of ventilationto blood flow, the {dot over (V)}/{dot over (Q)} ratio, that isapproximately the same, and normally about 0.8 at rest. This value of0.8 is likely to change, with exercise for example, but its uniformitychanges much less, ventilation is matched by the body to perfusion.

[0134] If {dot over (V)}/{dot over (Q)} matching is perfect it can beshown mathematically that the partial pressure of all gases of interestin the end expired breath (excluding the dead space, namely thebronchial tree, within which there is no gas exchange) is equal to thepartial pressure of those gases in the arterial blood. Moreover thesepartial pressures are the same in all parts of the lung.

[0135] {dot over (V)}/{dot over (Q)} matching is quite close to perfectin healthy young adult lungs. In childhood and in later life it is lessperfect.

[0136] In all people it is not perfect under anesthesia. Also in variousforms of disease and even in such body states as obesity it is likely toworsen. Thus in all human patients under anesthesia {dot over (V)}/{dotover (Q)} mismatch will be encountered, and when anesthesia is combinedwith age factors, body weight, and body position (lying flat is worse inthis respect than sitting or standing) and the effect on the lungs ofe.g. smoking, quite considerable degrees of it can be encountered.

[0137] It can be shown mathematically that in the presence of {dot over(V)}/{dot over (Q)} mismatch the partial pressure of a gas in theend-expired breath (excluding dead space gas, namely the first part ofthe expired breath) will no longer be equal to its partial pressure inthe arterial blood. It is reasonably close but it is no longer exactlythe same.

[0138] Prior art has accepted the errors inherent in this and a numberof published papers show reasonable agreement between the cardiacoutputs measured by prior art gas uptake methods of measuring thecardiac output and alternative methods of measuring it they have beentested against. The present method is expected to be capable ofdemonstrating reasonable agreement with existing methods that do notrely on gas exchange (thermodilution being the most widely used ofthese). A study in older and sicker patients where appreciable {dot over(V)}/{dot over (Q)} mismatch is expected has confirmed this.

[0139] However apart from technical errors {dot over (V)}/{dot over (Q)}mismatch remains a source of error that is unquantified. It is believedthat this problem may be overcome using one of the possible methods thata triple lumen tube makes possible.

[0140] While not wishing to be limited to theory it is believed that theinvention will give more reliable results if three alveolar volumedivisions are used on the basis of a technique which can overcome theproblem of {dot over (V)}/{dot over (Q)} mismatch.

[0141] Theoretical Source of Error

[0142] 1. {dot over (V)}/{dot over (Q)} mismatch is a phenomenonexhibited by all functioning lungs. If we consider a young adult lyingin the supine position there is a small discrepancy between the F_(N) ₂_(O), in the case of N₂O (as a soluble inert gas), as measured by a gasanalyzer in a gas sample taken from the end of expiration, F_(aN) ₂_(O), and the F_(N) ₂ _(O) of the blood that is draining the lungs,F_(aN) ₂ _(O). In this example the subject is breathing a gas mixture ofuniform composition into both lungs. The F_(N) ₂ _(O) (of blood) canonly be accurately measured by specialized techniques. The discrepancyis evaluated as A-aDN₂O.

[0143] If this discrepancy is sufficiently large it will interfere withthe accuracy of the measurement of {dot over (Q)}_(c) because theequation where {dot over (Q)}_(c) is derived contains the variablesF_(AN) ₂ _(OL) and F_(AN) ₂ _(OR). The variables which are readilymeasurable are taken to be equal to the equivalent variables in blood,F_(aN) ₂ _(OL) and F_(aN) ₂ _(OR) and the equation referred to should beproperly written with F_(aN) ₂ _(OL) and F_(aN) ₂ _(OR) in the place ofF_(AN) ₂ _(OL) and F_(AN) ₂ _(OR). It would be entirely impractical tomeasure the variables F_(aN) ₂ _(OR) and F_(aN) ₂ _(OL) directly as thiswould involve sampling blood from the pulmonary veins, deep inside thechest.

[0144] However this source of error can be entirely eliminated if allalveoli in a single alveolar division can be caused to have exactly thesame concentration of gases in them. The usual situation is that thereis a spread of concentrations of F_(N) ₂ _(O) within a division becausethere is a spread of {dot over (V)}/{dot over (Q)} ratios within thedivision. The term {dot over (V)}/{dot over (Q)} means the ratio ofventilation, {dot over (V)}, that a particular alveolus gets to itsperfusion, {dot over (Q)}. The value of F_(AN) ₂ _(O) found within itscontained gas mixture will be different from that found within anotheralveolus if the {dot over (V)}/{dot over (Q)} is different.

[0145] 2. Theory of Balanced Uptake

[0146] If however the component gases of the inspired gas mixture, inparticular the most abundant ones, N₂O and O₂, are entering the blood atthe same relative rate that they are being delivered to the alveolusfrom above, the rate at which these two gases are taken up by the bloodbecomes dependent only on the blood flow. The ventilation becomesirrelevant because in this case (and only in this case) the inspired gasmixture, the alveolar gas mixture, and the expired gas mixture becomeidentical in composition. This state is described here as balanceduptake.

[0147] It can be described mathematically and it is found that fornormal adult values of {dot over (Q)}_(c) and whole body {dot over(U)}_(O2), and F_({overscore (V)}N) ₂ _(O) may not be more thanapproximately 0.37 in value.

[0148] At this value of F_({overscore (V)}N) ₂ _(O) there is onepossible gas mixture that can be given to the subject that will producebalanced uptake. Below this value of F_({overscore (V)}N) _(O) and rightdown to a zero value of F_({overscore (V)}N) ₂ _(O) there are always twopossible inspired gas mixtures of O₂ and N₂O that can be given to thesubject that will result in balanced uptake occurring. AtP_({overscore (V)}N) ₂ _(O)=O for example the two gas mixtures are 0%N₂O and about 80% N₂O. As the P_({overscore (V)}N) ₂ _(O) rises toward0.37 the value of F_(IN) ₂ _(O) (the inspired N₂O level) rises from zeroin one mixture while it falls from 80% in the other, becoming the sameat Fv_(N) ₂ _(O)=0.37 where it comes to lie between 60 and 70%.

[0149] For complete balanced uptake, carbon dioxide (CO₂) also must beadded to the inspired gas mixture in physiological concentration.

[0150] It has now been discovered that the composition of the rightbreathing mixture, the “balanced-uptake” mixture, can be calculated froma knowledge of both the cardiac output and the mixed venous fractionalpressure of N₂O, F_({overscore (V)}N) ₂ _(O) (and also the hemoglobinconcentration).

[0151] It turns out that for F_({overscore (V)}N) ₂ _(O) values in therange that will be present in most patients, for every specific valuethere are two possible gas compositions, that is to say two possibleratios of nitrous oxide to oxygen in the balanced uptake mixture. Thisbeing the case it is possible to find these ratios simultaneously bytrial and error by using two lumens of a triple-lumen tube, one for eachof the two balanced uptake mixtures. The third lumen would ventilateeither a segment of a lung or an entire lung with a non-balancedmixture. The need for this arises because the value ofF_({overscore (V)}N) ₂ _(O) needs to be kept stable over time and underproper control.

[0152] Such a system ensures that the alveolar gas mixture in eachcompartment (whole lung or segment thereof is uniform in compositionthroughout that compartment and that the perfusing blood that leaves thecompartment (to mix with the blood leaving the other two compartmentsand form the arterial stream) has fractional pressure values of N₂O thatare the same as the F_(N) ₂ _(O) of the breathing gas mixture for thetwo balanced uptake mixture compartments.

[0153] Accordingly it is believed that this innovation would improve theprecision and accuracy of the method very considerably.

[0154] Referring to the drawings FIG. 1 shows a triple lumen cuffedendobronchial catheter 1 having a primary tube 2 which includes threelumens (not visible). The three lumens are for providing individual gasmixtures to the right upper lobe bronchus 3 feeding the upper lobe ofthe right lung 4, the right hyparterial (or right truncal) bronchus 5feeding the middle and lower lobes of the right lung 6, and the leftmain bronchus (or left lung bronchus) 7 feeding the left lung 8, asshown in FIG. 2.

[0155] At the top of primary tube 2 the three lumens become threeindependent connector tubes 9,10 and 11 which are located outside themouth when the catheter is in position within the trachea 12 of asubject. Primary tube 2 is molded with a bend 13 towards the center ofits proximal half designed to overlie the tongue posteriorly down to theglottic opening.

[0156] Distally there is a tracheal cuff 14 which, when positioned, liesentirely within trachea 12 and when inflated through inflation funnel 15firmly seals primary tube 2 within the trachea 12.

[0157] Immediately below the distal margin of the tracheal cuff 14outlet 16 of one of the internal lumens opens to the exterior of thetube on its left hand side and terminates. This outlet 16 is at thebottom of the end of the lumen fed by connector tube 11 and provides gasmixture to the left lung 8. Its upper margin 17 lies about 2 cm distalto the tracheal cuff 14.

[0158] Beyond the outlet 16 a tube 18 containing outlets 19 and 20curves to the right and slightly posteriorly. Outlets 19 and 20, whichare in the form of two lumens or tubes, extend from the lumens ofprimary tube 2 to which connector tubes 9 and 10 respectively areassociated.

[0159] Two centimeters below the lower margin 21 of outlet 16 and on theleft side is the upper margin 22 of a distal inflatable cuff 23. Thisupper margin 22 then encircles tube 18 obliquely such that in obliquecross section along the line of the margin of the cuff the margin 22extends proximally up the tube 18. On the tubes right side the margin isproximal to its level on the tubes left side by lcm.

[0160] The distal margin 24 of distal cuff 23 on the other handobliquely crosses tube 18 in the other direction so that on the rightside the margin 24 is distal by —3 cm end the width of the cuff 23 onthe right side is much greater than its width on the left hand side—3 cmwide compared with 1 cm wide on the left.

[0161] When in position distal cuff 23 lies around the right mainbronchus. The right hand part of the cuff 23 also extends into thehyparterial bronchus 5, which is the extension of the right mainbronchus beyond the origin of the right upper lobe bronchus 3.

[0162] On the right hand side of the tube 18 and centered midway betweenthe upper and lower margins of the distal cuff 23 outlet 19 opens to theexterior. Outlet 19 is elongated in the axis of the tube 18 andapproximately 6-8 mm long by about 1½-4 mm wide. The distal cuff 23surrounds opening 19 which opens into the upper lobe of the right lung4. The distal cuff 23 is firmly attached to the outer surface of tube 18to a distance 1-2 cm around the perimeter of opening 19.

[0163] One to two mm distal to the distal margin 24 of the distal cuff23 tube 18 terminates at outlet 20. The cross-section at outlet 20 isoblique as it is parallel with the oblique distal marking of the cuffand outlet 20 is consequently oval in shape.

[0164] The tracheal cuff 14 and the distal cuff 23 are inflated by twocuff inflating tubes 25 and 26 respectively which open into themdistally while proximally they extend within the body of primary tube 2(as two small additional mini lumens) toward the proximal bifurcations27 and 28 respectively. Beyond the bifurcations they extend 10 cm asindependent tubes. Within this independent part of each tube 25 and 26are pilot balloons 29 and 30 and at the proximal ends inflation funnels15 and 31, which may be replaced by cuff valves mounted beyond femaleLuer connections.

[0165] The respective internal diameters of the three lumens should be1:2:2 with the lumen feeding the right upper lobe being the smallest.

[0166]FIG. 3 is a diagrammatical representation of part of a preferredembodiment of the invention.

[0167] Notes:

[0168] 1. Tubes carrying gas are denoted thus: =

[0169] 2. Arrows alongside, or entering, or leaving denote direction offlows.

[0170] 3. Ordinary arrows (→) denote one direction only and increasingflow.

[0171] 4. Double ended arrows (⇄) denote respiratory flow i.e. tidal innature, with or without pauses of no flow, associated with inflation anddeflation of a division of the respiratory system.

[0172] 5. Electrical connections are denoted by single black lines. Thedirection of current is denoted by arrowheads on these lines (—).

[0173] A gas source of O₂ under high pressure 32 which may be containedfor example in a cylinder, passes gas through a gas regulator orreducing valve 33 into a conducting pipe where it is of some lowerpressure, 400 kPa being typical. From here it passes through a flowcontrol valve and a visual flow display 34 e.g. a rotameter. Beyond thisthe gas, now at just above ambient pressure, is joined by a similar flowof N₂O. The source of N₂O is also similar, high pressure supply 35, gasregulator 36, control valve and visual flow display 37. In addition theconducting pipe divides into two after the regulator 36 and the secondconducting pathway bypasses the control valve and visual flow display37. Instead it passes through a solenoid stepping valve 38 or similarelectronic flow control device capable of regulating flowrate inresponse to electronic signals, in this case coming from the computer39. It now rejoins the flow from the control valve and visual flowdisplay 37 and then joins up with the O₂ flow mentioned at just aboveambient pressure and also, in the case of divisional gas deliverysystems supplying the right upper division RULD and the right middle andlower lobes division RMLD, is joined by a pipe carrying CO₂ whose sourceis similar to that of O₂. It derives from a high pressure supply 40, gasregulator 41, and control valve end visual gas display 42 before joiningthe O₂ and N₂O gas flows at just above ambient pressure.

[0174] The combined flow now passes through anesthetic vaporizer 43, inthe case of the divisional gas delivery system LLD only, where it maypick up the vapor of a potent anesthetic agent at a dialed percentage ofthe flowrate through it.

[0175] The gas mixture with contained vapor of potent anesthetic agentif this has been added now passes past common gas outlet 50 intobreathing system 51 comprising breathing tubing of wide bore 52, 53, andbag-in-a-box patient ventilator 45 equipped with gas overflow mechanism55 designed to allow the concertina bag of the ventilator to remain gastight while it is filling (expiration) but tripping the gas overflowmechanism 55 as soon as it is full (at the top of its stroke) such thatfurther gas inflow after this point in time but before inspirationbegins escapes from the bag as ventilator bag gas overflow 56 which hasthe composition of FGFgas.

[0176] When inspiration begins gas flows from the concertina bag downbreathing tube 53 of wide bore into non-breathing inflating valve 54,down patient connection 57 and independent-part of triple lumen tube 58(consisting of one of independent-tube part of right upper lumen 9, ofright middle and lower lobes lumen 10 or of left lung lumen 11).

[0177] From here the inspiration passes into the appropriate alveolarvolume division where gas exchange takes place.

[0178] While the inspiratory gas is flowing toward non-rebreathinginflating valve 54 there is added an inflow of marker gas (1) toinspiratory gas at a steady flowrate 59. The inspiratory gas passesforward a sufficient distance for radial mixing to occur and is thensampled at a constant flowrate at sampling point, inspiratory gas (1stdivision) 60 which carries it to a solenoid (not shown) of solenoid bank(1).

[0179] Solenoid bank (1) is a solenoid bank consisting of threesolenoids passing FGFgas from each of the three divisions to gasanalyzer 49.

[0180] (Inspiratory gas is also sampled as it passes down patientconnection 57 but this sampling is not used for fear of contaminationwith expiratory gas which might fail to pass non-rebreathing inflatingvalve 54.)

[0181] Expiratory gas then passes back the same way as far asnon-rebreathing inflating valve 54. On its way it is sampled for thepurpose of determining individual gas concentrations present at the endof the breath at sampling point, inspiratory and expiratory gas (1stdivision) 61. The sample stream passes to a solenoid which is shown ofsolenoid bank (2) 44. This solenoid bank consists of three solenoidspassing inspiratory and expiratory gas from each of the three divisionsto gas analyzer 49.

[0182] Solenoids of the second solenoid bank, 44, which is shown, passinspiratory or expiratory gas along sampling lines 61, 46 and 47 of thethree divisions. Finally solenoids of the third solenoid bank, solenoidbank (3), also not show, pass EXHgas from sampling point expiratory gas63 of each of the three divisions, to gas analyzer 49.

[0183] After passing non-rebreathing inflating valve 54 it becomes gasdischarged from patient, 40, and has the composition of EXHgas whichreceives inflow of marker gas (2) 62. This is sampled as before, thistime to a solenoid of solenoid bank (3) which is not shown. It issampled at sampling point, expiratory gas (1st division) 63.

[0184] It is important that non-rebreathing inflating valve 54 be ofdemonstrable efficiency in its construction. Other makes of thesevalves, e.g. Ruben's valves were leaky and not suitable. Efficiency isimportant because retrograde flow leads to inaccuracy due to doublesampling.

[0185] Solenoids of solenoid banks (1), (2) and (3) open in rotation andclose at the same moment the next solenoid opens so that gas flowthrough the analyzer is continuous.

[0186] The gas analyzer should be a rapid gas analyzer capable ofdefining the expiratory wave form.

[0187] The solenoids are controlled by computer 39 through electricalconnections 64-72 inclusive. Gas analyzer signals are sent to thecomputer through lead-to-computer-lead 73.

[0188] Gas discharged from gas analyzer is lost from the system for mostanalyzers and must be accounted for as a spurious component of uptake inthe case of inspiratory gas sampled from the breathing system, 51, andof inspiratory and expiratory gas sampled from patient, connection 57.In the case of expiratory gas sampled from gas discharged from patient,40, the loss of gas does not need to be accounted for.

[0189] The whole operation of the system is conducted both manually andby operation of the computer 39. In an example of the operation of theapparatus shown in FIG. 3 the right upper lobe division, RUD 4, isventilated initially with a gas mixture containing 79% N₂O, 14% O₂ and7% CO₂.

[0190] The left lung division, LLD 8, is ventilated initially with 100%O₂ to which a potent anesthetic agent vapor (e.g. isoflurane) has beenadded by the anesthetic vaporizer 43 to produce a correct level ofanesthesia. Its ventilation has been adjusted to produce an end-tidalvalue (F_(ETCO) ₂ _(LLD)) of 0.05 to 0.055. The ventilation is monitoredby the system operator (in general, the anesthetist). The ventilation ofthe RUD 4 is then set at a level of ¼ of the level of ventilation of theLLD 8.

[0191] The right middle and lower lobe division 6 is ventilatedinitially with 0% N₂O, 93% O₂ and 7% CO₂. Its ventilation is set at alevel of % of the level of ventilation of the LLD 8.

[0192] After a period of five to ten minutes the following may be done.

[0193] From the inspired and end-tidal concentrations of N₂O in the RUD4 (F_(IN) ₂ _(ORUD) and F_(ETN) ₂ _(ORUD)) the inspired to end tidaldifference is calculated. The same is done in the RMLD 6. Thisdifference is called the I_(ETDRUD) and the I_(ETDRMLD). Thus:

F _(IN) ₂ _(ORUD) −F _(ETN) ₂ _(ORUD) =I _(ETDRUD)

F_(IN) ₂ _(ORMLD) −F _(ETN) ₂ _(ORMLD) =I _(ETDRMLD)

[0194] If I_(ETDRUD) is negative in value the flow of N₂O from its gasdelivery system (1) is reduced by the solenoid stepping valve (3). Thedegree of reduction is related to the type of breathing system. Thepreferred type is a non-rebreathing system. In this case the degree ofreduction is calculated, according to percent reduction of N₂O desired,by a formula:${{reduction}\quad {in}\quad {\overset{.}{V}}_{{FGFN}_{2}{ORUD}}} = \frac{\% \quad {reduction}\quad {desired} \times 0.01}{{current}\quad F_{{IN}_{2}{ORUD}} \times {\overset{.}{V}}_{{FGFN}_{2}{ORUD}}}$

[0195] where {dot over (V)}_(FGFN) ₂ _(ORUD) is the current fresh gasflowrate of N₂O in the RUD being delivered by the gas delivery system.

[0196] The percent reduction desired is the absolute value ofI_(ETDRUD).

[0197] After allowing a period (for stabilization of the new I_(ETD) ofup to a minute) the new I_(ETD) is evaluated. Stabilization may notactually occur if either F_({overscore (V)}N) ₂ _(O) or {dot over(Q)}_(c) are continuing to change but evaluation of the new I_(ETD)should still be done. On the basis of this, further adjustment of {dotover (V)}_(FGFN) ₂ _(ORUD) should be made in a similar way. IfI_(ETDRUD) is positive, {dot over (V)}_(FVFN) ₂ _(ORUD) should beadjusted back again, by increasing {dot over (V)}_(FGFN) ₂ _(ORUD)similarly, but it should be adjusted to increase F_(IN) ₂ _(ORUD) aboveits initial value of 79%.

[0198] If I_(ETDRUD) is positive and F_(IN) ₂ _(ORUD)=79% balanceduptake in the RUD(I_(IEDTRUD)=0) can be obtained by raising N₂O) flow tothe RMLD until I_(ETDRUD) is equal to 0.

[0199] This process may disturb the balance in the RUD and some back andforth tracking may be necessary between N₂O flow adjustment to the RMLDand to the RUD.

[0200] Small adjustments to the {dot over (V)}_(FGFN) ₂ _(ORUD) will bemore responsive in altering I_(ETDRUD) than equal increments ordecreases of {dot over (V)}_(FGFN) ₂ _(ORMLD) will in alteringI_(ETDRMLD) because of the mathematical relationship.

[0201] Furthermore because the RUD is the smallest division adjustmentsto it will least disturb the value of F_({overscore (V)}N) ₂ _(O). Assuch disturbance may take some minutes to manifest itself fully it ispreferable as a matter of policy to make adjustment to the {dot over(V)}_(FGF) first, wait for stabilization and then make adjustment to the{dot over (V)}_(FGFN) ₂ _(ORMLD) being guided by the value of theincrease in {dot over (V)}_(FGN) ₂ _(ORUD) achieved. The rise or fall ofthe value of F_(AN) ₂ _(ORUD) (end-tidal F_(AN) ₂ _(ORMLD) are likely tooccur together but in opposite directions after the initialstabilization because they are most likely to be caused by a change incardiac output or a change in whole body O₂ uptake. The ratio of therise in {dot over (V)}_(FGFN) ₂ _(ORMLD): rise in {dot over (V)}_(FGFN)₂ _(ORUD) is expected to be 15-20 over most of the range of F_(AN) ₂_(ORMLD) and F_(AN) ₂ _(ORUD) values (which are 0-65 and 65-80respectively approximately).

[0202] The strategy of adjusting the {dot over (V)}_(FGFN) ₂ _(ORUD)first can be computerized although probably it remains best to make theinitial stabilization manually. To this end manual adjustment undervisual control is made available but a parallel system of finer controlby a computer through a solenoid stepping valve is also provided in thepreferred system.

[0203] The initial process of adjustment of the two balance values to beselected, the higher one in the RUD and the lower one in the RMLD givesthe system operator the choice over a range of F_({overscore (V)}N) ₂_(O), higher F_({overscore (V)}N) ₂ _(O) values causing them to becloser together, lower ones farther apart.

[0204] The value of F_({overscore (V)}N) ₂ _(O) that determines this canbe set independently by allowing a flow of N₂O into the left lung fromits gas delivery system (positive value of {dot over (V)}_(FGFN) ₂_(OLLD)). The choice of F_({overscore (V)}N) ₂ _(O) to be selected is amatter of judgment.

[0205] The computer can be programmed to set a particular value ofF_({overscore (V)}N) ₂ _(O) a parameter which can be calculated fromQ_(c) once it is first known. It can be programmed to track and defendthis value through adjustment of {dot over (V)}_(FGFN) ₂ _(OLLD), and itcan be programmed to defend the balanced state in both the RUD and theRMLD by adjustments to both the {dot over (V)}_(FGFN) ₂ _(ORUD) and {dotover (V)}_(FGFN) ₂ _(ORMLD) when imbalance spontaneously appears.

[0206] The output of the computer, 39, to visual display 74, printout 75or RS232 interface 76 will go to other electronic devices, and/or anyother useful output modality and will also be capable of carryinginformation concerning any of the values of the various parametervariables observed by the measuring instruments or calculated from theirreadings and/or other data stored in its memory or communicated to itfrom other sources, e.g. manual input or RS232 communication from otherelectronic devices.

[0207] Numerical Example

[0208] Suppose that relevant variables listed below posses the statedplausible values: Inspired F_(N2O), left = 0.8 Inspired F_(N2O,) right =0 Alveolar ventilation left = 2 L/m Alveolar ventilation; right = {dotover (Q)}_(c)L = 2.5 L/m 2 L/m {dot over (Q)}_(c)R = 2.52 L/mF_(e,ovs V)N2O = 0.4

[0209] (The value of F_({overscore (V)}N) ₂ _(O) lies midway betweeninspired F_(N) ₂ _(O) on the left and inspired F_(N) ₂ _(O) on the rightif sufficient time has passed since the induction of anesthesia forsaturation of the body tissues with N₂O.)

λN₂O=0.5

{dot over (U)}_(O) ₂ _(R)=0.125 L/m

{dot over (U)}_(O) ₂ _(L)=O.125 L/m

[0210] The alveolar F_(N) ₂ ₂ _(O) on the two sides can now becalculated. Alveolar gas can be considered to be formed by the directmixture of two streams of N₂O-containing fluid. (This is true becausethe alveolo-capillary membrane separating blood from gas is freelypermeable to N₂O.) Let a mass balance equation be set up such that themass of N₂O carried into each lung is, equal to the mass carried away.Then:

F _(IN) ₂ _(OL) ·{dot over (V)} _(AIL) +Fv _(N) ₂ _(OL) ·{dot over (Q)}_(cL)·λ_(N) ₂ _(O) =F _(AN) ₂ _(OL)·({dot over (V)} _(AIL) +{dot over(Q)} _(cL)·λ_(N) ₂ _(O))

[0211] where F_(IN) ₂ _(OL) is the left inspired F_(N) ₂ _(O) andV_(AIL) is the left alveolar ventilation.$F_{{AN}_{2}{OL}} = \frac{{F_{{IN}_{2}{OL}} \cdot {\overset{.}{V}}_{AIL}} + {F_{\overset{\_}{V}N_{2}O} \cdot {\overset{.}{Q}}_{cL} \cdot \lambda_{N_{2}O}}}{{\overset{.}{V}}_{AIL} + {{\overset{.}{Q}}_{cL} \cdot \lambda_{N_{2}O}}}$Similarly:$F_{{AN}_{2}{OR}} = \frac{{F_{{IN}_{2}{OR}} \cdot {\overset{.}{V}}_{AIR}} + {F{{\overset{\_}{v}}_{N_{2}O} \cdot {\overset{.}{Q}}_{cR} \cdot \lambda_{N_{2}O}}}}{{\overset{.}{V}}_{AIR} + {{\overset{.}{Q}}_{cR} \cdot \lambda_{N_{2}O}}}$

[0212] {dot over (U)}_(N20L) and {dot over (U)}_(N20L) are calculatedfrom the equations:

{dot over (U)} _(N20L)=(F _(AN) ₂ _(OL) −Fv _(N) ₂ _(O))·{dot over (Q)}_(cL)·λ_(N) ₂ _(O)

[0213] and

{dot over (U)} _(N20R)=(F _(AN) ₂ _(OR) −Fv _(N) ₂ _(O))·{dot over (Q)}_(cR)·λ_(N) ₂ _(O)

[0214] Using the stated values for the variables on the right:

{dot over (U)} _(N20L)=0.307692 L/m

[0215] and

{dot over (U)}_(N20R)=0.307692 L/m

[0216] Thus expected uptake rates in normal human subjects in healthwill approximate 300 mls/min. (When tissues are not saturated with N₂O,uptake from the left will be somewhat increased. Output from the rightwill be somewhat decreased. The uptake rate at the start will beapproximately 615 mls/min on the left side with little output on theright. The uptake rate at ten minutes is approximately 340 mls/minuteand the right output is approximately 280 mls/minute. Thereafter uptakedeclines more slowly. At one and a half hours left uptake is only 25 mlsper minute greater than right output. Tissue uptake need-not beconsidered a serious cause of any loss in precision of measurement ofuptake and output.)

[0217] The calculated values for F_(AN) ₂ _(OL) and F_(AN) ₂ _(OR) aftertissue saturation are:

F_(AN) ₂ _(OL)=0.646154

F_(AN) ₂ _(OR)=0.153846

[0218] The cardiac output equation derived previously is:${\overset{.}{Q}}_{c} = \frac{{{\overset{.}{U}}_{N_{2}{OL}}\left( {1 + \frac{{\overset{.}{U}}_{O_{2}R}}{{\overset{.}{U}}_{O_{2}L}}} \right)} - {{\overset{.}{U}}_{N_{2}{OR}}\left( {1 + \frac{{\overset{.}{U}}_{O_{2}L}}{{\overset{.}{U}}_{O_{2}R}}} \right)}}{\lambda \left( {F_{{AN}_{2}{OL}} - F_{{AN}_{2}{OR}}} \right)}$

[0219] Inserting the values for the variables into this equation:$\begin{matrix}{{\overset{.}{Q}}_{c} = \frac{{0.307692\quad \left( {1 + \frac{0.125}{0.125}} \right)} - {\left( {- 0.307692} \right)\left( {1 + \frac{0.125}{0.125}} \right)}}{0.5\left( {0.646154 = 0.153846} \right)}} \\{= \frac{2 \times 0.615384}{0.5 \times 0.492308}} \\{= {5.00\quad L\text{/}{\min.}}}\end{matrix}$

[0220] Throughout this specification and the claims which follow, unlessthe context requires otherwise, the word “comprise”, or variations suchas “comprises” or “comprising”, will be understood to imply theinclusion of a stated integer or group of integers but not the exclusionof any other integer or group of integers.

[0221] Those skilled in the art will appreciate that the inventiondescribed herein is susceptible to variations and modifications otherthan those specifically described. It is to be understood that theinvention includes all such variations and modifications. The inventionalso includes all of the steps and features referred to or indicated inthis specification, individually or collectively, and any and allcombinations of any two or more of said steps or features.

1. A method for measuring the pulmonary blood flow in a subjectincluding: isolating two or more divisions of the respiratory system,said divisions comprising the complete gas exchanging part of saidrespiratory system; ventilating each said division with a separate gasmixture, at least one of said gas mixtures including an inert solublegas; determining uptake of inert soluble gas in at least two of saiddivisions; determining relative pulmonary blood of said divisions;determining end tidal concentration of inert soluble gas in at least twoof said divisions; and calculating pulmonary blood flow from determinedvalues of uptake and end tidal concentration of inert soluble gas, andrelative pulmonary blood flow.
 2. A method according to claim 1 whereintwo divisions of the respiratory system are isolated.
 3. A methodaccording to claim 2 wherein said two divisions comprise the left andright lungs respectively.
 4. A method according to any one of claims 1to 3 wherein said inert soluble gas comprises nitrous oxide.
 5. A methodaccording to any one of claims 1 to 3 wherein at least one of said gasmixtures comprises two or more inert soluble gases.